just stop…

Posted on Tuesday 28 April 2015

Well, this can’t be a book review of Lieberman’s and Ogasi’s Shrinks, the Untold Story of Psychiatry or Whitaker’s and Cosgrove’s Psychiatry under the Influence because I’ve read neither, but we all have a pretty good take on what they’re about. What struck me is that the titles could be interchanged, and they would still work. Lieberman’s book continues the well worn theme that the 1980 revolution ushered in by the DSM-III in which Psychiatry was liberated from Psychoanalysis and put on the path of true science – so he could’ve worked with a title like Psychiatry under the Influence. And Whitaker and Cosgrove could’ve gone with Shrinks, The Untold Story of Psychiatry to illustrate how much the post-1980 version of Psychiatry has been  influenced  dominated by the pharmaceutical industry. This weekend we were offered a tête-à-tête between the two with Dr. Lieberman’s appearance on the Canadian radio program – CBC: The Sunday Edition – promoting his book [the operative comments come at around 51:30]. The host, Michael Enright, had interviewed Robert Whitaker previously, and played the transcript, asking Dr. Lieberman to comment:
Lieberman: “Is [Whitaker] wrong? What he says is preposterous. He’s a menace to society because he’s basically fomenting misinformation and misunderstanding about mental illness and the nature of treatment. What he just said in that clip you ran about, if you’re taking an antidepressant and you go off it and you get sick again… the same thing could be said about insulin for diabetes and asthma medication… Whitaker, he ostensibly considers himself to have been a journalist, God help the publication that employed him, but he has an ideological grudge against psychiatry for whatever reason and there’s no, what he calls research is simply his opinion and his construction of information."
Enright: "What about his contention that the unmedicated patients did better than the medicated patients?"
Lieberman: "I’d say that’s absolutely wrong. If you do a controlled study with various illnesses, whether it’s schizophrenia, depression, bipolar disorder, obsessive compulsive disorder, and you do a randomized study, assign one group to receive whatever the state of the art is in psychiatry including medication and you assign the other to some innocuous, non-medical type of supportive therapy or whatever, and you follow the people for a period of time the outcomes will be extraordinarily superior in the treated group. The magnitude of the difference we can sort of quibble about, but there’s no doubt about it."
By that afternoon, there was a post about it on Mad In America, Lieberman Calls Whitaker “A Menace to Society”, and shortly thereafter, another by Robert Whitaker, A Challenge to Dr. Lieberman, saying:
So here is our challenge to Dr. Lieberman. Please provide a list of randomized studies that show that medicated patients have a much better long-term outcome than the unmedicated patients. Please note that we are asking for studies that measure outcomes over the long-term, say for at least two years or longer, and are randomized, since you indicate there are many such studies. Please point out the “extraordinarily superior” outcomes for the medicated group. We presume the studies will focus not just on symptom control, but also functional outcomes…
This is not the first time Lieberman has denounced me as a crappy journalist. [See CV here.] After Mad in America was published, we were on a National Public Radio show together, where he said that my book was a travesty that set journalism back decades [as apparently I had failed to get in line with the rest of journalists writing about the wonders of modern psychiatry]. He has written other things very similar to what he told Michael Enright on Sunday, but I have to confess, I took extra pride in being called a “menace to society.” I think one day I will put that on my gravestone.

Dr. Lieberman obviously sees himself as the champion and spokesman for Psychiatry. It seems to antedate his tenure as APA President. In September 2011, not long after the DSM-5 Task Force had to abandon the attempt to create a "biological" classification and it became apparent that PHARMA was closing its CNS Drug research labs, Lieberman recorded a MedScape video [Psychiatric Diagnosis in the Lab: How Far Off Are We?] about the neuroscience breakthroughs that were just around the corner. He has continued to be a cheerleader for APA and his own brand of Psychiatry [DSM-5: Caught between Mental Illness Stigma and Anti-Psychiatry Prejudice, Our Time Has Come, Psychiatry Hits its Stride as Brain Science Informs Treatment], and has continued to push for a strong relationship with PHARMA [Don’t Turn Your Back on Industry, but Keep It Honest, APF Convenes Unique Pipeline Summit, Time to Re-Engage With Pharma?]. One could make the case that he is the leading [or at least the loudest] voice for the Guild of Psychiatry.

The outbursts at Robert Whitaker are not Dr. Lieberman’s only ventures onto the slippery slope of contemptuous ad hominem attacks. In February when the British Psychological Society released Understanding Psychosis and Schizophrenia, Tanya Luhrmann, an anthropologist, wrote a New York Times op-ed supporting the BPS report [see Redefining Mental Illness and which side of the street?…]. Dr. Lieberman responded in another MedScape piece with a similar ad hominem that indicted both Luhrmann for writing  it and the New York Times for publishing it [What Does the New York Times Have Against Psychiatry?]. Said Liebermann:
The article about mental illness was an incredibly unscholarly, misinformed, confused — at worst, unhelpful, and at best, destructive — commentary that will add to the confusion about the diagnosis of mental illness, enhance the stigma, and may lead some patients to doubt the veracity of the diagnoses that they have been given and the treatments that they are receiving…

Finally, when I read the article, disappointed and annoyed as I was, I tried to write a serious, responsible, and constructive letter to the editor, which I submitted within 24 hours. Seventy-two hours have elapsed since the article’s publication. I haven’t heard from the Times about their interest in publishing my response, so I assume they won’t publish it. The name that I publish under is my own. My credential is the Chairman of Psychiatry, Columbia University College of Physicians and Surgeons, one of the leading departments of psychiatry in the country, past president of the American Psychiatric Association, and author of the forthcoming book for the lay public called Shrinks: The Untold Story of Psychiatry.

Assuming that my letter was not completely uninformed or incoherent, I would think that there would have been reason to accept it, given my credentials and the fact that I made a reasonable point. Let’s see if they print it. If they don’t, that adds further to my dismay over what I consider to be journalistically irresponsible behavior by this once-respected newspaper.
It’s hard to comment on Dr. Lieberman’s remarks without following the Talion Law [an eye for an eye, and a tooth for a tooth] like saying that he attacks and discounts, but doesn’t address the content of the criticismor by pointing out the arrogance of his comments about Robert Whitaker as a journalistor his petulant remark about the New York Times’ journalismor his believing that his credentials entitle him to speak for psychiatry at large. All of those are ad hominems. And that’s all I can think of to say, so I’ll just stop. I wish he had…
    April 28, 2015 | 10:48 PM

    Lieberman says “f you’re taking an antidepressant and you go off it and you get sick again… the same thing could be said about insulin for diabetes and asthma medication….” implying that, like diabetes and asthma, antidepressants correct a physiological problem — in short, “chemical imbalance” redux.

    That statement also suggests he is unaware of the frequency of withdrawal syndrome, how it is almost invariably misdiagnosed as relapse, and how it has confounded studies of antidepressant efficacy and the true rate of relapse after discontinuation.

    James O'Brien, M.D.
    April 29, 2015 | 12:31 AM
    Bernard Carroll
    April 29, 2015 | 1:55 AM

    I will stick to what I know best, which is mood disorders, and I will call Robert Whitaker’s attention to a classic study of maintenance antidepressant treatment. [Pub Med ID # 2244793]. It ran for 3 years; the patients were randomized to maintenance treatment with (1) placebo plus clinic checks; (2) psychotherapy plus placebo; (3) psychotherapy alone; (4) psychotherapy plus imipramine; or (5) clinic checks plus imipramine. There were massive differences in relapse rates. After 3 years the relapse rates in groups (1) through (5) respectively were 89%, 74%, 67%, 27%, and 24%. Patients taking active drug did much better, whether or not they were receiving structured psychotherapy. There are similar data for prevention of recurrence in geriatric depression over 3 years with nortriptyline [Pub Med ID # 9892449]. These examples undercut the insinuation by Whitaker that maintenance drug treatment cannot possibly have any benefit over the long term. They clearly establish proof of that principle. And I haven’t even touched yet on the long term preventive benefit of lithium treatment for patients with bipolar disorder.

    April 29, 2015 | 2:10 AM

    The diabetes argument never ceases to baffle me. If you don’t take antidepressants you will most likely not die from ‘serotonin shortage’. In fact, the label says they increase suicidal thought. Go off your ‘Lantus’ for a while and see how you fare. No wait. Please don’t do that. Stupid bad comparison.

    April 29, 2015 | 9:12 AM

    Me thinks those who protest the loudest have the most to conceal for their shortcomings. Lieberman is the poster child for why no one with a conscience or honest committment to psychiatry should be a member of that organization known as the APA.

    People seem to think my accusations of what is antisocial are too over the top at times, well, if the financial agenda is so corrupt and harmful to patient care, what is that then?…

    James O'Brien, M.D.
    April 29, 2015 | 11:43 AM

    These two deserve each other.

    One is like the President of the Natl Association of Realtors denying that homes can ever be in a bubble and you should buy a house at any price with zero down while the other claims there is no value to ever owning a home and you should spend your whole life renting.

    I get that humans are inclined toward extremism and overstatement but it’s painful to watch intelligent, supposedly self-actualized intellectuals fall into this trap.

    April 29, 2015 | 2:46 PM

    It is good that Bernard Carroll is pointing out a longer term study that points to the benefit of medication. And I hope he does get started on writing posts about the long term preventive benefit of lithium as well. This would certainly be something to weigh when considering the grave health effects of lithium for many people.

    Robert Whitaker has been asking psychiatrists to do this all along- for years and years. He has laid out all his research in a very concise and accessible format on his website and asked people to respond to it. He has been trying to promote real and honest conversations that could lead to truthful reporting so that patients and their family could have informed consent about treatments.

    Don’t psychiatrists understand that as a result of all the lying and corruption and the ‘paternal’ attitude that permeates the profession, many clients have so little faith and are truly terrified by treatment. They may like and believe that their psychiatrist is truly trying to help them, but mistrust the ‘system’ under which psychiatrists seem to get their information, because many ‘good’ psychiatrists do not speak out against the misconceptions, the corruptions, nor admit to the contradictory or incomplete nature of the current research. The profession does not give patients ‘ true informed consent’ as is expected in other areas of medicine.

    For example, instead of Bernard Carroll saying ‘These examples undercut the insinuation by Whitaker that maintenance drug treatment cannot possibly have any benefit over the long term’, why doesn’t he say here is an example of long term maintenance that works although there are other studies that have shown
    that drug maintenance for some population may be harmful. More research is needed.

    Why make it a personal attack against Whitaker.

    Aren’t psychiatrists grateful that he is trying to ferret out what effective treatment looks like.

    What has made me so sad is how silent or defensive most psychiatrists have been about Whitaker’s work. Where are all the comments from the many caring, responsible psychiatrists who do have patients on long term medication that are not functioning well? What many people who do not have experience with ill friends or relative believe, is that patients on medication are doing well, and those who are not on medication are dangerous and scary. And now that Ronald Pies is saying that no responsible psychiatrist ever believed in the chemical inbalance theory, where are all the comments from honest psychiatrists saying ‘actually we did use to say that a lot as we thought it was so important for our patients to stay on their meds, or because we believed it’.

    The psychiatry profession needs Whitaker to help restore people’s faith in the profession. I so wish there were more psychiatrists like 1 boring old man who does seem to speak up regularly and often in a way that is certainly moving the profession forward. And I think James O’Brien is very wrong in saying that ‘these two deserve each other’. Whitaker is truly trying to search for truth in psychiatry and maybe he would ‘just stop’ if more responsible and caring psychiatrists would ‘just start’ a little more.

    April 29, 2015 | 5:40 PM

    Sorry Dr. Carroll, but your study is so poor that no serious person would rely on its data. For one, all patients were first treated with imipramine, meaning that placebo “relapse” would include lots of patients undergoing imipramine withdrawal. And the trial was apparently not blinded – which could go a long way to explaining the ridiculously low relapse rates for the drugs that are not seen in blinded trials. That study just has no credibility.

    April 29, 2015 | 5:42 PM

    I meant double-blind, not just blind.

    April 29, 2015 | 5:47 PM

    Reading more, it’s not clear whether the study was double blind and I do not have access to the full text. Regardless, there was no real blinding because of the study design. The patients in the study all first responded to imipramine during “acute” depression. They were then randomized to one of the five cells. Everyone in the placebo arm would have recognized when they were taken off the drug. And the doctors would know as well. Also, by using only those who responded to imipramine, you bias in favor of the drug and probably biased against placebo. Just a crummy study overall.

    April 29, 2015 | 5:55 PM

    Correct, undiagnosed withdrawal syndrome confounds almost 100% of studies of antidepressant efficacy where any of the subjects were discontinued in order to assess rate of relapse.

    The undiagnosed withdrawal syndrome make relapse rates appear to be higher than they ought to be, and masks an important adverse effect that is under-recognized even by expert psychiatric researchers.

    A dead horse that simply will not stay dead when antidepressant efficacy is discussed.

    April 29, 2015 | 9:03 PM

    These people who comment here who just rail away about psychiatry prescribing to patients without alleged regard or concern for consequences, you all are so disingenuous and dishonest to try to pin the blame solely on psychiatrists.

    And you know it at the end of the day, because if you honestly include the copious conspirators that are a sizeable number of patients who just demand drugs, then your cause would be rejected outright, because you would offend the audience you desperately want and need to sustain your agenda.

    I watch patients EVERY DAY dismiss my sincere and heartfelt recommendations to be in therapy and problem solve their psychosocial issues that often are concurrent reasons they seek out mental health care. So, maybe just once, someone here who is an MIA supporter might surprise us and admit that the pinata in the room is not just psychiatry, but, American culture run amok looking for quick fixes.

    But, as some of the posts at MIA of late are blatantly advertising, the need is just blind faith your narrative has unchallenged merit. Yeah, good luck with that once people who are not looking to just join a mob ask more questions and are skeptical when the answers just don’t jive with the accusations!

    You want honest, sincere, and long lasting healthy change? Address everyone who is complicit to the problem! Interesting how the issues in Baltimore seem to be bringing out the same dialogue by those who want real change for the better, and not just stoking partisan agendas, by both sides of the polluted aisle of Republocrats!

    Extremist zealot opportunists, that is what drives much of dialogue to debates these days. And those who know better don’t call these faux “benefactors” on the frauds they really are!

    Lieberman and Whitaker aren’t the ones who should set the tone for the debate about appropriate mental health care. Am I the only one who sees this for the fraud it is by them and their legions!?

    James O'Brien, M.D.
    April 30, 2015 | 1:02 AM

    I have been fiercely critical of Dr. Lieberman but I’m sure he is aware of discontinuation syndromes.

    Since you’re holding people to such high standards, I’d like to know in your video when you talk about epilepsy from discontinuation at 4:45, was that something you measured with EEG telemetry and did you get prolactin levels as a secondary confirmation measure? I would expect nothing less from a world’s expert.


    Since we all know the answer stop misrepresenting yourself as a world’s expert. And please no more snide comments about Harvard Deplin research that you can’t possibly understand.

    Bernard Carroll
    April 30, 2015 | 2:49 AM

    It’s nice to see so many comments about the prevention study with imipramine. Some commenters opined without being familiar with the full report of this study. A careful reading will reveal the excellence of the study’s design and execution. The bottom line is that this study gives clear proof of principle for preventing recurrences of major depression with medication over 3 years.

    As for the magnitude of the effect, a picture is worth a thousand words. The Figure shown above with my original comment says it all. Try to spend some time getting familiar with the information on display there. For instance, the difference in 3-year cumulative recurrence rate between the placebo-clinic checks group and the imipramine-clinic checks group is 65%. That translates into a Number Needed to Treat (NNT) of 1.5 for imipramine to prevent recurrences over 3 years. Nothing to sneeze at. That compares with NNT = 3-4 for treatment of a current episode with imipramine, and NNT = 9-11 for treatment of a current episode with SSRI antidepressants. NNTs below 2 are seldom found in therapeutics. Like I say, nothing to sneeze at.

    One can also see from the Figure that the separation between the groups continued to increase far beyond the early discontinuation period of, say, 3 months. Because they are typically self-limited, it is not plausible to claim that a discontinuation syndrome explains the increasing group differences over 3 years.

    As for questions raised about the design, clinicians and evaluators were strictly blinded to drug versus placebo assignment of patients. The patients also were blinded. Some, but by no means all patients would guess they had been switched to placebo, as the tapering occurred over 3 weeks rather than abruptly.

    The objection that all patients had previously responded to imipramine does not hold water. That is exactly what one would require for a long term prevention trial with randomized discontinuation. Commendably, the authors waited until the recovered patients had demonstrated stable improvement over 17 weeks in a continuation phase before beginning the 3-year randomized maintenance phase of the study.

    Another design issue to note is that the authors required that patients be in at least their third lifetime episode of depression, and with 2 episodes in the last 2.5 years, when entering the study. The patients had on average experienced repeated episodes of depression every 2.17 years for 12.5 years, and the time between episodes was progressively shortening (as is well known for the natural history of recurrent depression), so at the time of enrollment they were experiencing a new episode every one to two years. In fact, the median time between the end of the previous episode and the beginning of the index episode was just 25 weeks. This requirement for demonstrated frequent recurrences adds to the cogency of the study. Against that background there is no reason to be dismissive of a 3-year recurrence-free survival rate of 76% in the imipramine-clinic checks group. Looking for potential methodologic confounds is reasonable, but failing to acknowledge a major effect when it is staring us in the face (Figure) is not reasonable.

    April 30, 2015 | 8:44 AM

    It would be great if someone knew where I could find the full text of this study so I can read it and analyze it in more depth.

    But based on the abstract and Dr. Carroll’s description, I do not find the design to be adequate, let alone excellent. The fact is that tapering the patients off the drug will not eliminate the presence of withdrawal “relapse”, particularly when they have been on the drug for 17 weeks prior. Also, researchers rarely ask (or at least report) about placebo unblinding, but we know from studies that do that up to 80+% of patients and 90+% of clinicians can correctly guess their treatment (in antidepressant trials). The design of this study – using only patients who were both long term drug users and had recently stabilized on 17 weeks of the study drug, virtually guarantees that blinds will be broken – at percentages possibly approaching 100%. Pretty pictures are useless when the data they portray is flawed.

    In addition, given the extensive depression background of these patients, they were likely suffering from tardive dysphoria. They fit the profile exactly given their many years of depression treatment and the description of their depressions getting closer and closer together. If I wanted to study the acute effects of heroin, I would not line up a study filled with junkies who had been on heroin for years. Otherwise I would conclude that heroin is essential to daily functioning. Antidepressants are obviously not heroin, but that principle is precisely what these study authors have done. The insidious effect of past drug use is one reason why studies should prefer subjects with first episode depression or at least drug naive. And this is also something I worry about a lot these days – the poisoning of clinical trial data due to the near impossibility of finding appropriate subjects who have not been ingesting large amounts of psychoactive drugs for many years.

    The only legitimate way to test effectiveness and relapse rates of drugs is to randomize treatment during the acute phase of the trial, using drug naive and/or first episode patients. Even then there will be a lot of unblinding, but researchers should account for this by assessing whether the blind was maintained at trial end (and/or using an active placebo).

    April 30, 2015 | 10:07 AM

    I want to thank Bernard Carroll and Ryan for discussing and debating the merits of a long term study -one that took place over 3 years rather than `weeks’ . This is what many of us lay people want to believe is happening – that many long term studies are being conducted and debated until finally one day we will have more solid answers about treatment than we have today.

    Robert Whitaker
    April 30, 2015 | 11:05 AM

    Just a couple of notes on this, mostly in response to Dr. Carroll’s comment.

    a) I think it is great that Dr. Carroll has identified a study that he sees as proving the long-term benefit of imipramine. That is the whole point of this discussion: we need to have a full look at the evidence related to the long-term effects of psychiatric medications.

    I know the study referred to by Dr. Carroll, and reviewed it when I was researching Anatomy of an Epidemic. The first author was Ellen Frank, and it is titled: “Three-year outcomes for maintenance therapies in recurrent depression.” This was a study of patients with recurrent depression. 230 patients were enrolled into the study, and all then went through a two-week “drug washout” period, meaning they were taken off their antidepressant. All of the patients were then put back on imipramine and given interpersonal psychotherapy as well. Those who then responded to this combination treatment and remained “relatively symptom free” for a total of 20 weeks were then randomized into the actual “maintenance study.”

    In short, this is a maintenance study of a small subset of chronic patients who have stabilized well, for a fairly lengthy period, on imipramine and interpersonal therapy. (128 of the initial 230). In terms of medication, the 128 were then randomized to either continue receiving imipramine or to no medication or to placebo. Those who continued to get imipramine indeed had a much higher survival rate, over the three years, than those who were withdrawn from their antidepressants.

    So, what does this study show? Within the context of the discussion raised on Mad in America, Dr. Carroll points to it as evidence that antidepressants improve the long-term course of depression. Fine. In fact, I think this is precisely the type of study that psychiatry has generally relied upon for evidence that its drugs provide a long-term benefit. But, from my perspective, this study does not provide evidence of a long-term benefit at all. What it shows that if you take a group of chronic patients, and then run them through a treatment regimen that finds a smaller group who have stabilized well on imipramine for a fairly lengthy period (in other words, a select group of good responders to imipramine), that that group is then less likely to relapse if maintained on that drug than those withdrawn from it.

    The problem with this study, in my opinion, is that it tells us nothing about the long-term course of unmedicated depression versus the long-term course of medicated depression, and particularly in terms of functional outcomes. It tells you that if you run a study in good responders to a psychiatric drug, and then randomize patients to either continued drug treatment or to placebo (or no pill), that the drug-maintained group will have a lower relapse rate, with this lower relapse rate in this study lasting throughout the three years. But such relapse studies involve patients whose brains have been changed by the drug, and are now going through drug withdrawal following randomization. And while Dr. Carroll dismisses the idea that this increased risk would persist over a longer period of time, there are in fact researchers now worrying about persistent withdrawal effects, that may last for years (and perhaps indefinitely), precisely because the brain may not renormalize.

    So, again in my opinion, this is not a study that supports Dr. Lieberman’s contention on the Enright show that there are numerous randomized studies that show that psychiatric medications provide a long-term benefit. This shows something else. But, it’s good to have the discussion and the review of the evidence offered in support of Lieberman’s contention, and perhaps many people will agree with Dr. Carroll that it shows evidence that antidepressants improve the long-term course of depression.

    b) Dr. Carroll mentions that I believe that “maintenance treatment cannot possibly have any benefit over the long-term.” Just for the record, I don’t believe that at all, and have never said such a thing. I believe that psychiatry needs to figure out for whom the drugs work, and for how long, and while they try to address that question, that they should confront the evidence that I believe shows that antidepressants, on the whole, worsen the long-term course of depression (starting from the first episode.) I think there is evidence that this treatment, again on the whole, increases the chronicity of the disorder. But that is a very different statement that saying that “maintenance treatment cannot possibly have any benefit over the long term.” Maintenance treatment may very well have some benefit for a select group of people with depression, but that is different from saying that the drugs improve the long-term course of depression (compared to the natural spectrum of outcomes.)

    c) As for my new book, co-written with Lisa Cosgrove, Psychiatry Under the Influence, this came out of a fellowship I had at Harvard University, in a lab devoted to studying institutional corruption. And while we do write about pharmaceutical influence on psychiatry, the real focus of the book is how the APA and academic psychiatry—the institution of psychiatry we were asked to study—were corrupted by psychiatry’s own guild interests since the publication of DSM-III. The pharmaceutical influence is a distraction from this internal problem within the profession, and I have to say, we believe that the “institution of psychiatry” remains quite oblivious to how this guild influence has corrupted its behavior, in terms of fulfilling its ethical duties to serve the public, over the past 35 years. Anyway, that is what is “new” about this book: It really focuses on the guild interests of psychiatry, once it promoted its biological model, and how guild influence has led the institution astray. It is also meant to be a “case study” of institutional corruption, as opposed to a story only about psychiatry.

    April 30, 2015 | 12:52 PM

    Thank you Robert Whitaker for adding your insight and for striking a better tone than I did with my original post. I get frustrated by this issue a lot and have to tame my incredulous responses. Thank you Dr. Carroll for offering this study as an example, and like Robert Whitaker, I encourage you to give more examples.

    It is very hard to critique a study when you only have access to the abstract, though given the medium and the short time, I felt it necessary to try. Many of my points were getting precisely at what Robert states about long term withdrawal and this study’s focus on a very specific subset of patients who did well on imipramine. I also added the additional information about placebo unblinding, which I believe is important, but I know Robert has not written a whole lot about (or at least emphasized) in his books.

    Bernard Carroll
    April 30, 2015 | 6:07 PM

    First, to Ryan: Should you not have given the report a conscientious, independent reading before coming back with more misleading opinions and errors of fact? You still haven’t read it! We don’t know who you are or what your credentials are for your statements. Why should we give them credence? That’s always a problem with anonymous commenters.

    What you claim about withdrawal relapse doesn’t hold water. You need to read the detailed description of how recurrence was determined. And, even if you want to assert without evidence that all those recurrences out from 3 months through 36 months are withdrawal relapses, which is completely implausible, you would still need to account for the prevention of recurrences in the patients who stayed on imipramine, compared with their histories leading up to the study. There, too, there is a very large positive effect of the drug over 3 years.

    You went on to speculate about tardive dysphoria. What you say about that is off-target. Most readers haven’t heard about that concept. It arose first in relation to tardive dyskinesia, a motor disturbance that is caused by antipsychotic drugs. Tardive dysphoria was theorized to be an emotional counterpart of the motor disturbance seen in those patients. That meaning of tardive dysphoria is not in play in this discussion, because antipsychotic drugs were not in play. The second meaning of tardive dysphoria is more recent. It was suggested to be an effect of long term antidepressant drug treatment, and to be manifest as chronic, treatment-resistant depression. That was an admittedly speculative proposal and, to be kind, it has not attracted significant attention or confirmatory data. Your suggestion that the patients in the study suffered from tardive dysphoria is contradicted by the fact that they did indeed respond fully to imipramine in the index episode. Thus, they did not have the chronic, treatment-resistant form of depression that was proposed for tardive dysphoria. They did not “fit the profile exactly.” Perhaps you are confusing chronic depression with frequently recurrent depression.

    When time permits – probably tomorrow – I will come back with thoughts on Robert Whitaker’s comment.

    passer by
    April 30, 2015 | 11:56 PM

    As a rare casual observer here…

    I must say you could go back twenty years and hear/read the same arguments and debates written everywhere.

    My only question is this: if Psychiatry is so vested in the theoretical hypothesis that mental health maladies are biological based illnesses, and thus support the drug treatment modality; why hasn’t the hard core APA psychiatry (Pharma Cheerleaders) been able to produce any definitive concrete evidence to support their claims after all the future is now diatribe, similar nonsensical hoopla, and their infamous DSM bluster?

    As all these decades pass without any of the promised advances or real evidence; I would have to conclude that finally psychiatry is being seen more and more each day as the boy that kept crying wolf.

    I would have to say in my opinion that this slow and painful adjustment to reality is long overdue..

    big mouth
    May 1, 2015 | 12:31 AM

    I’m curious to know how other drugs factored in for the imipramine study. Most people hop around from one drug to another, so how many of those people were taking imipramine as a first-time ever antidepressant? For how many of those people was it the 4th or 5th antidepressant they’ve taken? I’m sure that matters, I don’t see how it couldn’t.

    It seems to me that one single study is not nearly enough to determine long-term efficacy of antidepressants, considering there are countless types of antidepressants. Wouldn’t you need to have the same exact study for every drug (at least every class of drug) to truly determine long-term efficacy of antidepressants?


    That’s just antidepressants.

    Here’s a monster list of psychiatric drugs (aka medicine) http://en.wikipedia.org/wiki/List_of_psychiatric_medications_by_condition_treated

    May 1, 2015 | 5:32 AM

    Big mouth-
    These studies were done when there were fewer drugs on the market. It was the pre-Prozac era. But the point Robert Whitaker has made is that the group studied was a group who had already had a history of chronic and persistent depression and they had already been exposed to at least nortryptiline. To then take them off the drug and study outcome only gives us information on this defined population responds over time. It is a different question as to what would be the three year outcome for people presenting with depression for the first time treated with and without drug.Also, as Dr. Nardo has written about recently, in the era in which this study was done, stricter criteria for depression was used. So it is also a different question as to what the three outcome would be for people with milder forms of depression treated with and without drug. So many more people today are exposed to these drugs. Now even the short term efficacy for many of these people has been brought into question yet many remain on these drugs for a very long time.

    May 1, 2015 | 8:43 AM


    Thanks for responding. Dr. Lieberman’s comments hardly reached a level deserving much scientific debate. This was a rant, similar to his Medscape response to Tanya Luhrmann’s recent NYT piece. He, at least, toned it down in his Dr. Oz comment today:


    I still wince when you say, “I believe that psychiatry needs to …” as if psychiatry is a unitary, personified entity. We wouldn’t say “journalism” or “psychology” in the same way. You’re taking about a subgroup of psychiatrists, not all of us. I would agree that subgroup exists and is way too large for my liking. That’s why I write about them too. That usage is widespread, particularly among the bloggers on Mad in America. I understand that many of them do, in fact, want psychiatry to go away altogether, but the “straw man” arguments aren’t the best way to say that.

    May 1, 2015 | 9:03 AM


    Not to get too sidetracked from this conversation but in my opinion, I think you’re taking things a little too personally when you take issue with Bob staying that “psychiatry needs to”. On one sleep apnea board I frequently visit, there a is similar type conversation regarding the sleep medicine industry because patients are quite tired of subpar treatment. I just think it is human nature when you are frustrated with a profession to speak in that type language without meaning to imply that everyone is bad in that field.

    Back to regularly scheduled programming.

    May 1, 2015 | 10:45 AM

    Dr. Carroll: I would love to give the report a full and conscientious reading, however I do not have access to it and obtaining it through my local library will take a week or more. What my “credentials” are should not matter unless we are just appealing to authority.

    My comments on the trial design were based on the abstract and your own comments. It appears that your comments were not very specific and you keep introducing new aspects of the design, so I will probably not comment further on the design until I can actually read the study. However, my description of relapse withdrawal is not wrong. Plenty of the patients could have been going through withdrawal based on Robert’s description of the study and your description. It is impossible to rule that out.

    Your assertion that this is not the case because the study cells continued to separate in the period of 3 – 36 months has serious flaws – namely that withdrawal is not the only factor in play here. As I said before, this study design guarantees unblinding. It selects long term drug users who would be generally familiar with the side effects and general sensations of an antidepressant. Then it withdraws those patients from their drugs. And then starts them all on the study drug. After a period on the study drug, it then removes some of them from the study drug. Do you think ANYONE in this study had any trouble knowing whether they were randomized to placebo or drug? The number who remained blinded is surely very small. And I would be surprised if the clinicians remained blinded for a single patient.

    As for tardive dysphoria – this is not a new concept. You describe it as associated with tardive dyskinesia originally, but I have not seen that. Instead, what you describe as the “more recent” version was proposed in the 1960s. The mechanism was described in the 1990s. Only recently has there been much study. The paper you link to is a good one, but I also think you are mistaken in your belief about the term. Tardive dysphoria describes any dysphoria that is delayed or appears at some later date. It is not restricted to patients who are treatment-resistant, as you assert. It has been discussed in that context largely because those patients are the most obvious examples of the phenomenon. But any person who suffers from a permanent dysphoria when antidepressants are removed can be said to have tardive dysphoria, regardless of whether they still respond to antidepressants. In essence, tardive dysphoria simply describes a long term withdrawal that occurs beyond what most would consider the normal withdrawal period. Tardive dysphoria as you describe is simply the end state on a continuum of decline that begins with a long term dysphoria when not on the drugs and ultimately, with enough time and dose, ends with a dysphoria even when on the highest dose of antidepressant. As for whether tardive dysphoria is real – I would expect that any honest psychiatrist would admit that it is. People have been describing it a very long time. Of course, some deny it, much as many of those same people denied the existence of withdrawal effects completely for decades.

    To summarize, I am not saying all the patients had withdrawal relapse, or all the patients had tardive dysphoria. What I am saying is that undoubtedly some of them did, and it is impossible to tell who or how many. The study design did not control for this, and it virtually guaranteed placebo unblinding. Given this, the study design was not adequate and is not a good study for what you claim. There are other far superior study designs available – even at the time this study was performed – that could have and should have been chosen if the authors wished to perform a more accurate assessment.

    May 1, 2015 | 11:41 AM

    Hi Bernard –

    I’d like to draw your attention to these two studies:

    1) Wunkerink’s 7 year study of medicated versus non-medicated outcomes for first-episode psychosis; here is the entire study:

    In this study, the people who went off medication did far better than those who stayed on it. Interestingly, there were no significant differences between the groups in terms of symptomatic remission, but a large difference (46% vs 19%) in terms of functional improvement favoring the non-medication group.

    With that in mind, how was outcome in your 3-year study assessed? Was it primarily symptomatic, or functional? I too would like to see this paper but have not been able to find it

    2) Harrow’s 15 year study of on-antipsychotic versus off-antipsychotic outcomes for people labeled schizophrenic; here is the whole study:


    Again the functional outcomes for the unmedicated persons were far better than they were for the ones who stayed on medication (about 40 vs 17%).

    So here are two studies arguing in the opposite direction to the notion that long-term medication use is beneficial for persons in severe mental distress.

    But, do these studies really prove anything? I think we should be more humble about the ability of one or two quasi-experimental studies to “show” that X or Y is true. Blinded or unblinded, randomized or non-randomized, one or two studies of human subjects don’t really prove anything. There are so many other uncontrolled variables going on, even in randomized, double-blinded studies of human subjects, that we would need many more such studies to show a strong trend.

    At best, one or two such studies begin to suggest a trend or a need for further, larger-scale, more rigorous follow-ups in future studies. Surely you (and Robert) know this…. in this regard I think we need to step back from the trees and see the forest a little more.

    Lastly, I agree with Ryan and Robert about a major problem in the study you identified (Bernard). It makes little sense to me that they only take a smaller group of people who initially respond well to Prozac, letting go of all the ones who did not respond, and then out of that smaller group, they keep some on the drug and take some off…. to me that is clearly biased. Wouldn’t it be more objective and complete to test the whole beginning group over the long term, rather than only a biased subset of those who responded well or perhaps in some way need the drug? Your responses so far on that question have not truly answered it; at best, such a study could show that in a small non-generalizable subgroup of people who respond well to Prozac, they may need to continue it over the long term.

    I am sure you can find problems with the studies I cited too, only one of which is randomized, I think. Nevertheless, the presence of these studies set against the ones you mentioned shows that we are not very close at all to answering the question about how effective long-term medication treatment for various types of emotional distress are.

    Bernard Carroll
    May 1, 2015 | 12:14 PM

    Robert Whitaker’s comment had three sections. The first section ran on for over 600 words but contained no linear argument, just recapitulations and a series of tendentious opinions. It mainly tells me that Robert Whitaker doesn’t understand the concept of proof of principle that I had emphasized. In the second section, he says he does not in fact believe that “maintenance treatment cannot possibly have any benefit over the long term.” That is good to see. He goes on to assert that nevertheless antidepressant drugs mainly worsen the long term course of depression, starting from the first episode. That is completely untrue of the classical antidepressant drugs given for the classical diagnoses. I can agree that current antidepressant drugs don’t match the classical drugs on efficacy for the classical diagnoses, and that most of the people given the current drugs don’t have the classical diagnoses, but then I have never carried a brief for the SSRIs or for the DSM system. The third section of Robert Whitaker’s comment was a promotional paragraph for his new book, and I will not comment on that.

    May 1, 2015 | 2:21 PM

    Who said Lieberman surely recognizes withdrawal or discontinuation symptoms/disabilities?

    Lieberman did an Ask Me Anything (AMA) on Reddit recently.

    This is what he thinks of those who have suffered under the psych meds:

    “The only thing that I can say about scientologies antipathy against psychiatry is that unlike the idealogical zealots like Robert Whitaker and patients who are unwilling to acknowledge their own illness and thus blame psychiatry. ”

    (emphasis added)


    That is slander and also abuse.

    And then, this:

    “I am very bullish on the future of psychiatry. Once we dispel the stigma it will be an enormously popular and much sought after field of medicine, maybe even rivaling plastic surgery, haha.”

    Oh, ha ha ha. The other destructive branch of medicine (cosmetic, a subset of plastic surgery)

    May 1, 2015 | 3:50 PM


    I would like to bring up one more critique of all of these studies.

    Here are the reliability ratings for major conditions listed DSM 5, IV, and III:


    Inn the first image, we can see that the reliability rating for Major Depression is most recently 0.32 (little better than chance agreement), and before that it hovered around the 0.55 mark, which is still poor, meaning that frequently psychiatrists disagreed as to in whom and when depression was or was not present.

    Does this consistently poor reliability for major depression – and many other conditions – not undermine the whole basis of the study you cited, as well as the ones I did? I don’t see how these studies’ results can be considered reliable and valid, if they are not based on a condition which psychiatrists can identify reliably.

    I think too many people are accepting that psychatric studies are based on reliable identification and classification of distressed human experience, when that is arguably not at all the case. Based on these type of reliability problems, one could argue that the whole field of psychiatric study is a pseudo-science.


    May 1, 2015 | 3:54 PM

    Joel Hassman, your remark is the disingenuous one.

    “These people who comment here who just rail away about psychiatry prescribing to patients without alleged regard or concern for consequences, you all are so disingenuous and dishonest to try to pin the blame solely on psychiatrists.”

    Yes, I blame psychiatrists and MDs who harm patients, deny responsibility, and dismiss adverse effects. They write the prescriptions. “The culture” does not. Many people who comment on MIA are there because a doctor disabled them and called the new disability an underlying condition. It’s criminal.

    If surgeons did what psychiatrists do they’d go to jail. They don’t decide on a surgical plan based on shiny leaftlets or whim, and they don’t perform unnecessary surgeries because patients or the culture wants them to. When they screw up, they pay. They don’t say “The missing kidney, and that fresh incision? She was like that when she got here.”

    May 1, 2015 | 8:19 PM

    After watching all the BS in Baltimore this week by the antisocials who ended up controlling the politicians here in town, I just want to draw the analogy to the antipsychiatry folk here, like CLC above and the most recent comment by AA taking on Mickey here who had responsibly noted that not all of psychiatry is complicit to the Lieberman agenda, we as honest and responsible providers aren’t going to be harassed or intimidated by the ongoing insincere and irresponsible commentary that is led by your leader Dr Whitaker, who shows no real responsibility reigning in the onslaught by the legion who troll his site Mad In America.

    Yeah, that last sentence is a bit of a run on rant. But, so is the BS that goes on here post in and out, when these folks just want to claim anyone who does not condemn psychiatry is a loser and accomplice. I live outside Baltimore, and have had to endure this week of hostility and pathetic overgeneralizations and defense of inappropriate violence and condemnations of the police and society in general.

    Yeah, I think the parallels to extremism of political partisan agendas to what is being regurgitated by the antipsychiatry folk has strong ties. And responsible folk should not only reject this narrative, but condemn it for what it will lead to if not realized for it’s inherent failure. Liebermans and their choir ilk do not help the profession of psychiatry, but, this outright rejection and shrill cries for it to be abolished in its entirety is just another example of why turning to the polarized opposite of clueless and poorly conceived rebuttals to bad care interventions does not help the public at the end of the day.

    Wanna bet that at least half of the antipsychiatry folk also pine for police to be abolished too? And isn’t that an interesting correlation as well? Authority to the antipsychiatry crowd is just not acceptable when agendas that are not so healthy and respectable would be exposed to your hopeful supports from the general public yet to be claimed, eh?!

    Whatta week this has been for me and the American people.

    Oh, and by the way CLC, surgeons have been known to screw up too, so will you pine for that profession to be abolished too???

    May 1, 2015 | 9:52 PM


    You would make people respect you more, and would represent your profession better, if you responded in a measured, calm way. As you must know, that can be done by clearly stating your points while contesting those points of the opposition that you feel are unfair, but avoiding shrill rhetoric of your own and not stooping to the level of the people that you feel are attacking you or your profession. In your message above, rather than appearing stronger than the person you are arguing against, you frankly look like a child shouting back at other children.


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